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A Two-year Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis.

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ClinicalTrials.gov Identifier: NCT03203850
Recruitment Status : Recruiting
First Posted : June 29, 2017
Last Update Posted : January 28, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

The purpose of this study is to evaluate the efficacy and safety of deferasirox film coated tablet (FCT) versus phlebotomy for the management of iron overload in adults with HH at risk of iron-related morbidity. This evaluation will provide information on the two treatment options in terms of the rate of response of proportion of patients reaching the study target SF ≤ 100 μg/L and their associated safety profiles.

In addition to exploring the safety and efficacy of deferasirox FCT in hereditary hemochromatosis (HH), this study is being conducted to fulfill an FDA post-marketing requirement [PMC 750-10 (Exjade) /PMR 2888-8 (Jadenu)] to provide additional randomized data to confirm the ocular safety profile of deferasirox through detailed ocular assessments in patients treated with deferasirox FCT for 2 years.


Condition or disease Intervention/treatment Phase
Hereditary Hemochromatosis Drug: Deferasirox FCT Procedure: Phlebotomy Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Open-label, Randomized Two-year Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis.
Actual Study Start Date : January 11, 2018
Estimated Primary Completion Date : March 10, 2022
Estimated Study Completion Date : March 10, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemochromatosis
Drug Information available for: Deferasirox

Arm Intervention/treatment
Experimental: Deferasirox FCT Arm
randomized in a 2:1 ratio: Deferasirox to surgery
Drug: Deferasirox FCT
Taken orally once per day (QD)
Other Name: ICL670

Experimental: phlebotomy
randomized in a 2:1 ratio: Deferasirox to surgery
Procedure: Phlebotomy
according to investigator's decision




Primary Outcome Measures :
  1. Proportion of patients achieving target SF ≤ 100 μg/L for the first time. [ Time Frame: Response is defined by achieving target SF ≤ 100 μg/L on or before 24 months. ]
    Assess the response rate (RR) of deferasirox film coated tablet (FCT) and phlebotomy treatment arms where response is defined by achieving target serum ferritin (SF) ≤ 100 μg/L on or before 24 months. Estimate of the RR and corresponding 95% confidence interval (CI) will be provided for each arm. No formal hypothesis testing is planned in this study.


Secondary Outcome Measures :
  1. Incidence of ocular adverse events (AEs) overall [ Time Frame: 24 months ]
    To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by the incidence of treatment-emergent ocular adverse events (AEs) (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.

  2. Incidence of ocular adverse events (AEs) by severity [ Time Frame: 24 months ]
    To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by AE severity (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Written informed consent must be obtained prior to any screening procedures.

Patients eligible for inclusion must meet all following criteria prior to receiving study treatment:

1. Male or female ≥ 18-years-old 2. Documented genotype testing confirming homozygous for the C282Y mutation (C282Y/C282Y) 3. Transferrin saturation ≥ 45% (at either screening visit) 4. Serum ferritin (SF) ≥ 500 μg/L (at either screening visit)

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Exclusion Criteria:

  1. Medical conditions that preclude inclusion:

    • Iron overload not due to HH
    • Condition which might significantly alter the absorption, distribution, metabolism or excretion of oral deferasirox
    • Systemic disease which prevents taking study treatment or any contraindication to phlebotomy
    • Inflammatory condition or immunological disease which may interfere with the SF interpretation, such as an active infection, collagen vascular disorders, irritable bowel syndrome, lupus, or immune thrombocytopenia
    • Significantly impaired gastrointestinal function or disease that may significantly alter the absorption of oral deferasirox, e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection.
    • Psychiatric or addictive disorder which prevent giving informed consent or undergoing any of the treatment options or unwilling or unable to comply with the protocol
    • Uncontrolled or significant cardiac disease or symptomatic cardiac arrhythmias, e.g., sustained ventricular tachycardia and clinically significant second or third degree AV block without a pacemaker.
    • Illicit drug use and/or alcohol use, defined as an average alcohol consumption greater than one standard drink a day for women or two standard drinks a day for men within the 12 months prior to enrolment. A standard drink is generally considered to be 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80-proof distilled spirits
    • Cirrhosis, including Child-Pugh class A, B, and C, diagnosed by liver biopsy, elastography, radiologic exams, or clinical criteria
    • Active hepatitis B or C (hepatitis B carrier will be allowed)
    • History of HIV seropositivity (ELISA or Western blot)
    • Organ transplant recipient
    • Malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, except localized basal cell carcinoma of the skin, or any history of hepatocellular carcinoma
  2. Concomitant therapy that precludes enrollment:

    • Prior iron chelation therapy
    • Prohibited concomitant medications with deferasirox
  3. Abnormal Laboratory Values:

    • Significant anemia that contraindicates phlebotomy (males with hemoglobin < 130g/L, females with hemoglobin < 120g/L) in both screening visit samples
    • Platelets ≤ 50 x 109/L in both screening visit samples
    • Urine protein/urine creatinine ratio > 1.0 mg/mg in both non-first void urine screening visit samples
    • Creatinine clearance ≤ 40 ml/min, or use the locally approved contraindication limit in prescribing information if it is stricter, in both screening visit samples
    • Serum creatinine > 1.5 x ULN in both screening visit samples
    • ALT ≥ 5 x ULN in both screening visit samples
    • Total bilirubin > 1.5 x ULN in both screening visit samples
  4. Participation in an investigational study:

    • Observational registry study is allowable
    • Within 30 days prior to enrollment or within 5-half-lives of an investigational product, whichever is longer
    • Treatment with a systemic investigational drug within 4 weeks or topical investigational drug within 7 days of starting the study
  5. Pregnancy and contraception:

    • Pregnant or nursing (lactating) women
    • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless using basic methods of contraception, such as:
    • Total abstinence Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are unacceptable methods.
    • Female sterilization (bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. If oophorectomy alone, hormone levels must confirm menopause.
    • Male sterilization (at least 6 months prior to screening). The vasectomized male must be the sole partner.
    • Barrier methods of contraception: condom or occlusive cap For UK: spermicidal foam/gel/film/cream/vaginal suppository
    • Placement of an intrauterine device or intrauterine system
    • Women considered as post-menopausal and not of childbearing potential are allowed to be enrolled in the trial if they have had 12 months of natural (spontaneous) amenorrhea with an expected clinical profile, e.g., age appropriate and history of vasomotor symptoms.

Other protocol-defined inclusion/exclusion may apply. -


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03203850


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

Locations
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Belgium
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
Spain
Novartis Investigative Site Recruiting
Manresa, Espana, Spain, 08241
Novartis Investigative Site Recruiting
Barcelona, Spain, 08041
Novartis Investigative Site Recruiting
Madrid, Spain, 28007
Switzerland
Novartis Investigative Site Recruiting
Lugano, Switzerland, 6900
Novartis Investigative Site Recruiting
St Gallen, Switzerland, 9007
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03203850     History of Changes
Other Study ID Numbers: CICL670F2203
First Posted: June 29, 2017    Key Record Dates
Last Update Posted: January 28, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
hereditary hemochromatosis
ICL670
deferasirox FCT
iron overload
Additional relevant MeSH terms:
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Hemochromatosis
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Iron Overload
Iron Metabolism Disorders
Metabolic Diseases
Deferasirox
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action